Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases

Predictors of possible exposure to rabies in travellers: A case-control study.

Background: Timely administration of post-exposure prophylaxis (PEP) can prevent rabies. For non-vaccinated persons, PEP consists of multiple vaccinations and rabies immunoglobulin (RIG) on indication. Since RIG is scarce, the need for PEP could be restricted through preventing animal contact and pre-exposure vaccination. We aimed to identify determinants for possible rabies exposure among travellers to provide more targeted pre-travel advice. Method: A case-control study was performed. Cases were defined as persons with a possible rabies exposure (category II or III injury according to WHO classification guidelines) in a rabies endemic country. Controls did not report exposure during travel. Multivariable logistic regression was performed. Results: 229 cases and 1427 controls were included. Predictors (p < 0.05) of possible rabies exposure were young age, male sex, travelling to Western or Southeastern Asia, visiting a monkey park, pet ownership, previously visited the same country and considering oneself an experienced traveller. Negative predictors were travelling for business, visiting friends and relatives, and fear of animals. Conclusions: Pre-travel advice should take the identified predictors into account to provide better targeted information and pre-exposure prophylaxis